One step toward normal heart beat by biological pacemaker

Zeinab Neshati,1,* Negar parizadeh,2



Cardiac electrical impulses are generated in sinoatrial node (san) which establishes spontaneous action potentials. san contains pacemaker cells which are responsible for generation of initial electrical impulse during each heartbeat. degeneration of these cells or san is irreversible and can result in heart failure and death.


The pubmed and web of science, were searched for relevant studies published from 2015-2017.


Although electronic pacemakers are effective for san dysfunction, they have some defects including inadequate autonomic modulation, limited battery life and infection which lead scientists to think of a more physiological alternative, like biological pacemakers. so far, different strategies have been devised for creation of biological pacemakers based on cell and gene therapy. desired genes are either transcription factors or pacemaker characteristic genes like hyperpolarization-activated cyclic nucleotide–gated (hcn) channels, t-boxes gene family (tbx2, tbx3, and tbx18), connexins gene family (cx40, cx43 and cx45), shox2 and trpc3. as hcn channels play a prominent role in generating unique pacemaker current (if, funny current) and directly respond to autonomic stimulation via binding to camp, the most promising functional results have been derived from those studies in which viral delivery of different isoforms of this gene have been performed through injection into the conduction system.


Although, great progress has been made in creating biological pacemakers and many promising results have been achieved from animal studies, there is still room to bring to light some critical aspects of biological pacemakers before they can be adopted for clinical applications.


Sinoatrial node, biological pacemaker, genetic intervention, hcn channels, clinical application